Interpreting mixed signals: the cell's cytokine conundrum

Cytokines are essential for the activation, differentiation and control of the immune system. Many cytokines, alone or in combination with other cytokines, have multiple functions and can often act on many different cell types with distinct developmental or functional consequences. Despite the myriad of cytokines and cytokine receptors, there are relatively few signaling molecules that transduce these diverse cytokine signals. In this review, we will discuss the potential mechanisms used by cytokines to mediate distinct cellular outcomes from a small number of signaling molecules. Understanding this paradigm in cytokine signaling can aid in the development of potential therapeutic approaches involving cytokine targeting or use.

► A myriad of cytokines drive diverse responses but utilize few signaling molecules. ► Signaling via the same STAT can have diverse downstream consequences. ► Receptor, signaling and/or epigenetic modulation shapes the cytokine response. ► STAT3 illustrates how a single molecule can orchestrate diverse cellular events. ► Future studies should use focused, targeted mutations assayed using global approaches.